Proton treatment : the new magic cure ?

This article talks about how proton treatment has become the new rage in cancer treatment. This is inspite of soaring costs of treatment and little data to prove that it is actually better. The biggest selling point of proton treatment is that it can be made to focus on the tumor unlike X-rays which would damage a lot of surrounding tissue as well.

Technorati Tags: cancer,proton

HIV news

1. Yet another HIV vaccine bites the dust.. Rather oddly they took another month to discontinue vaccinating volunteers in South Africa. Also the spokeswoman for the trials describes the failure as "a sad day for the industry". Maybe I am mis-understanding her, but that seems quite a self-centred viewpoint to take. It seems there are more than two dozen vaccines being tested for safety in human trials and only one of those is ready for testing its efficacy.
2. A shocking article linked to the discontinued vaccine : people vaccinated with the Merck vaccine may actually be at an increased risk for contracting HIV. Of the more than 3000 volunteers vaccinated with the experimental vaccine- they found 24 cases of HIV infection as compared to 21 in the placebo group. I do not know the significance of the data (and it appears neither do the experts so far)- but Merck and NIAID are quick to reassure the public that the vaccine itself is incapable of causing infection. A spokesperson from the AIDS vaccine advocacy coalition hopes that this data will not scare away future volunteers for prospective HIV vaccines.
3. The CDC now recommends regular HIV testing for TB patients. This follows data from 2005 that show that almost 1/3rd TB cases have not been tested for HIV. Of those tested in 2005 13% were HIV positive.

1. About bras and exercise : apparently most of the bras available nowadays don't really limit breast motion during exercise- hence do not offer adequate support to the breast. Acc. to the article, the most effective are the molded cup/encapsulation bras which limit all types of breast movement.
2. Previvors and preventive Mastectomy : this is a pretty moving story of a young woman with a BRCA1 gene mutation. What would you do if you knew you had a 60 to 90 % chance of developing breast cancer and a 50% chance of getting ovarian cancer? If removing your breasts would reduce the risk by 90% and removing your ovaries would halve the risk - would you opt for either..or both or would you wait and watch? Its a longish article- but worth the read.
3. Human or not? : The New Jersey Supreme Court has ruled that a doctor is under no obligation to tell a pregnant woman that she is carrying “an existing human being” before performing an abortion. Somehow I am still annoyed by the article.. The whole concept of being pro-choice is that an informed woman can make decisions that best suit her..is it fair to say that this woman was not or rather did not feel informed enough? On the other hand, it is a moral judgement that should not have to be pushed on to a doctor..And if a doctor was forced to pronounce a fetus of any age human or not (as per his very human capabilities)- then the woman just had to believe him or find another information source. The whole situation is very repeatable and not going away anytime soon..

Free Burma!

Free Burma!

International Bloggers' Day for Burma on the 4th of October

International bloggers are taking action to support the peaceful revolution in Burma. We want to set a sign for freedom and show our sympathy for these people who are fighting their cruel regime without weapons. These Bloggers are planning to refrain from posting to their blogs on October 4.

We are joining this.

NEJM -- September 27th,2007

NEJM -- Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years

The NEJM this week carries a report on a cohort study that assessed the impact of thiomersal (a mercury containing preservative in some vaccines) on neuropyschological outcomes in children aged 7 to 10 years. The bottom line of the study is that there is no association between exposure to thiomersal between birth to 7 months of life and neuropsychological functioning. You can read the entire article here.
However, there are certain subtler interpretations that need to be cited from the study. Tics seem to be associated with exposure to thiomersal in patients from one HMO (whether they differ in any way from the rest of the cohort is not addressed) and this replicates studies done earlier in the US and Britain. This is probably something which needs to be looked into for the future.
The excellence of the study lies in their rigorous measurement of exposure to thiomersal, assessment of 42 neuropychological outcomes and measurement of possible confounding factors that may affect developmental status of the child.

If you are treating patients with cardiovascular disease with statins to lower their LDL cholesterol level, HDL cholesterol levels are still a significant inverse, predictor for cardiovascular disease outcomes even in patients with lowered LDL levels. That's the message of this NEJM article, which tried to answer whether lowering levels of LDL cholesterol with statin therapy might cover the risk posed by low levels of HDL cholesterol. The study suggests that HDL by itself is an important factor to control in patients on statins.

You know about HLA matching before transplants, now these researchers believe that antibodies against another set of molecules expressed on endothelial cells are associated with graft rejection. These new molecules are called MICA and because of their absence on PBMC's are not detected during cross-matching tests before transplants.

There is a great perspective article by Dr. Sugarman on the development of a Vaccine Court in the US. This has arisen from the number of claims filed by parents for vaccine-related injuries and autism following vaccination. The article outlines the history of the Vaccine Injury Compensation Program (VICP), which is a federal body set up to protect vaccine manufacturers from vaccine-injury related law suits. The article highlights how little proof is required to prove causation of vaccine related injury.
In the VICP context, proof of causation does not need to be shown to the extent of what some
might call scientific certainty.Rather, it suffices to prove causation according to the civil-law standard of “the preponderance of the evidence,” showing that causation is “more likely than not.”

Another article, which is also a public forum for posting your own view on the issue, is a personal account on the detachment physicians develop during their professional careers and our inability to express emotions of sympathy, compassion and involvement in our patients' lives or deaths. A physicians' life goes on from one case to the next, micromanaging and compartmentalising a patients life into smaller diagnostic or treatment conundrums and more often that not, peer pressure and implied standards of professional demeanour prevent us from vocalising common feelings.

BMJ 22nd September,2007

Following the resounding failure of the MTAS selection system for postgraduate medical training posts in the UK, there has been an inevitable outcry about the unemployment faced by UK medical graduates. To read about the debacle that is the MTAS, read Parashkhev Nachev's account in the BMJ. He explains how the system was flawed from the outset by ignoring evidence based practice in the design of the scheme. He also appropriates blame to the Royal College, who are meant to be the safeguards of the professions' interest.

There are many who blame the growing numbers of International Medical Graduates for robbing home graduates of their duly entitled jobs. This week's BMJ has a debate on the issue authored by two senior consultants who completed their undergraduate training outside the UK.

Dr. Edward Byrne, dean of biomedical training at UCL argues that training posts must go to UK graduates irrespective of merit and only in the event of a shortage (which did not happen this year) should other candidates be asked to fill these posts. Read the full article here. In response, Dr.Edwin Borman refutes this suggestion in the belief that restricting access would damage the future of the profession. Read his commentary here.

The most interesting article in this journal this week, perhaps published either because it reflects the sentiments of many UK graduates and citizens or because of its controversial direction is written by Graham Winyard, retired postgraduate dean of the Hull-York medical school.
The article condones the MTAS system and blames the british government for lacking a comprehensive and firm anti-migration policy for doctors. His suggestion would almost stop any IMG from going to the UK.
"The most obvious action would be to suspend the skilled migrant programme as it applies to doctors and establish a two stage recruitment process similar to that used in other countries,whereby overseas applications are considered after those of domestic graduates (which in our case would have to include Europe)."

I am utterly shocked that UK medical professionals are willing to insulate themselves from the world's medical community. There is no doubt that jobs are scarce and a combination of expanding medical schools, influx of IMG's, poor workforce planning and a non-functional computerised selection process has only highlighted the problem. However, the answer cannot be to cocoon yourself but rather to learn from other systems that have similar issues.

How would you expect to advance if you breed practices and knowledge incestuously? A closed,non-competitive system is bound to stagnate if not driven by a need to excel in a global setting. I can only presume that Dr. Winyard foresees and is content to herald the death of meritocracy (as little as it remains in the UK medical system today) and a multicultural NHS workforce in the near future if the government follows his suggestion.

On a personal note, I love the UK and foresaw myself as a medical professional in the NHS, but I am glad that I walked away from them this year. Although I did not predict such a catastrophe, I was convinced that IMG's would find it hard to work through the system to reach consultant positions. The prevailing antagonism towards IMG's from senior consultants, who are part of the selection panels, will only make it harder to find good training positions in the NHS in the near future. I would advise IMG's to look elsewhere for opportunities for the next couple of years

Hospitals may examine Patients for HIV/AIDS without Permission

This is terrible! I cannot believe clinics and doctors are allowed to do this especially as there seems to be no scientific rationale behind the argument.

The clinics suggest that blanket testing for HIV prevents health care workers from getting infected. Surely, health care workers should probably be aware of HIV transmission pathways which includes transmission by infected blood, unprotected sexual intercourse,mother-to-child either by breast feeding or during delivery. Which of these are these clinics worried about?

If you are really worried about infected needle stick injury, that could happen accidentally when you are taking a blood sample. So, you have to take precautions anyway prior to the HIV test result being known. Existing standards in clinical practice expect medical workers to take precautions to reduce needle stick injury or contamination with blood products as routine.

There are rather obvious confidentiality issues and patient rights that are being violated and while the article mentions these issues, the article fails to highlight the poor clinical standards that forms the basis of this policy and the possibility of a dangerous,covert problem of discrimination.

1. If clinics are having to test patients for HIV to avoid infection of their workers, this could only happen if current practices preventing HIV transmission do not exist in these clinics. This is even more worrisome especially if private clinics charging patients exorbitant fees and claiming the best current medical practice are presently not enforcing simple,cheap HIV and infected blood transmission prevention measures.

2. Clinics believe they need to take special precautions if a person is HIV+. This is on the slippery slope to overt discrimination. Where would these special precautions end? Would private clinics treat HIV+ patients differently? Could private clinics refuse treatment to patients who are HIV+? Would clinics be allowed to test for any disease? See this story about HIV discrimination by hospitals.

The entire idea of having universal precautions against infected blood precautions is to avoid this sort of discrimination. Although we know that such discrimination exists, health workers must lead the fight to abolish such discrimination not reinforce it by such ludicrous policy.

Of course, the article does not tell us who has legislated this policy, who ratified it, where it is applicable. But, even if such a policy does not exist, the very thought of such a policy should make us shudder.

An interesting article reviewing the choices that physician-scientists have had to make over the ages and how it is affecting current MD/PhDs. The article highlights that physician research is becoming a difficult career option and there are fears that it might jeopardize medical discoveries of the future.

Some interesting stuff going on..

1. An afternoon nap is good for the heart : "Those who took naps of more than 30 minutes three or more times a week had a 37% lower risk" of heart-disease related death. This seems to be more beneficial in working men (64% reduced risk) as compared to non-working men (36 % reduced risk). Not enough female deaths occurred to get figures for female risk reduction. Obviously, there is the additional factor.. the sort of people who manage to fit in an afternoon nap are the less likely to be stressed individuals/Type A people, making them less likely to indulge in other stressful behavior that could lead to heart disease. So, is mid-afternoon sleep by itself beneficial (in any person type) or is it the sort of person who decides to sleep in the middle of the afternoon who is doing himself a favor ? Like Dr Dimitrios Trichopoulos says "Its worth studying further."
2. Doctor links microwaveable popcorn to bronchiolitis obliterans : It seems heated diacetyl, a compound found in synthetic butter and food flavoring when inhaled can cause small airway scarring over a period of time. The patient in this case liked the fragrance of heated popcorn so much that he would often inhale the fragrance immediately after making himself a bag. Also, he had eaten microwaved popcorn at least twice a day for more than 10 years. The NY times article further states that "Exposure to synthetic butter in food production and flavoring plants has been linked to hundreds of cases of workers whose lungs have been damaged or destroyed." But characteristically "Producers of microwave popcorn said their products were safe." The man in question stopped eating popcorn and his lung function improved in as little as 6 months. I smell a lawsuit in the making..
3. "Designer vaginoplasty" may be dangerous : If you watch E! channel (I do!!) then you know what this is about. Even last week on Dr. 90210 I saw a bit of an episode where a woman had a perineal surgery to possibly tighten her butt and her vagina (?). I didn't hang around long enough to find out.. But similar procedures to "tighten areas altered by aging and childbirth" are " not medically indicated" cites the American college of Obstetricians and Gynecologists. Surprise surprise !! What I didn't know (I guess this borders on gossip ) was that the famed Dr. Matlock who has treated at least 3000 women was placed on probation after a malpractice suit in 2000. Anyway, his training course (for other aspiring plastic surgeons) costs more than 50,000$ and he has trained 140 doctors. Wow- thats quite some money to have made on a procedure that has not been proven to be of any benefit, is not backed by scientific studies and has quite a bunch of potential risks!!

Insulin pumps and more about insulin

This article has all the information...including pros & cons of using insulin pumps, recent and future developments in the world of insulin pumps. Quite an interesting read.

Some interesting facts about insulin :

1. Insulin abuse: No, I'm not talking about Munchausen's by proxy. This is when insulin is used to increase muscle mass either by itself or in conjunction with GH to increase muscle mass in body-builder types.
2. It is the only animal protein to have been made in bacteria in such a way that its structure is absolutely identical to that of the natural molecule.
3. It is currently manufactured in yeast cells.. yeah the very yeast that are responsible for the bread which raises the glycemic state of the body(Yeah- this may be a convoluted connection- but I'm amused anyway!).
4. The patent for insulin was sold to the University of Toronto for one dollar.
5. C- peptide (the peptide connecting the two chains of the human proinsulin molecule - absent in commercial insulin preparations) has been shown to increase adenosine-induced myocardial blood flow(+ 35%) and LV function (+5%), stroke volume (+7%) in type 1 diabetics (albeit in a study involving only 10 men).
6. It has also been postulated that C-peptide has a therapeutic effect on diabetic neuropathy, nephropathy and artery repair.

It somehow adds up. Why would a specialized machine like the still-altogether-mysterious human body manufacture one protein just to hold two other proteins chains together ? It seems almost logical that the third protein- in this case- the C-peptide would have a function of its own. It is not present in commercial preparations of insulin. Maybe we need to include it too in the future ?

Another question nagging away at the back of my head - is it ethical for patent laws to apply to insulin manufacturers ? Isn't it sadly inhumane to hold on to 'trade secrets' that prevent newer forms of insulin from being cheaper and more accessible ?

Idiopathic Pulmonary Fibrosis

aka cryptogenic fibrosing alveolitis. Prevalence : 5 million worldwide and 200,000 in the US. It affects men and women (1 : 2) and there is some genetic predisposition (3% show familial clustering). There is also a strong association with (current or prior) cigarette smoking.

This is one of those diseases that does not have a real established cause (hence "idiopathic") or even a real cure ( this despite the fact that there are newer treatments and the usual corticosteroids and cytotoxic drugs given in such cases.) So what does a doctor really do ?

The chances of spotting this disease in its earlier stages seem scarce. Like most 'idiopathic' diseases - its diagnosis begins with exclusion. Till the disease is advanced the patient may only present with non-specific symptoms (dyspnea, dry cough) and signs (fine dry bibasilar inspiratory crackles aka Velcro crackles and clubbing). You order a CXR, a pulmonary function test and a HRCT. The HRCT especially is helpful in uncovering parenchymal disease and underlying carcinomas.

The confirmatory diagnostic test (in case of an indeterminate HRCT) remains a lung biopsy- that too an open surgery or video-assisted transthoracic surgery involving a multiple site biopsy - which in itself must be stressful to an already stressed patient.

What do I look for ?

1. CXR showing diffuse reticular basal and peripheral opacities, honeycombing and dilated airways d/t traction bronchiectasis.
2. Pulmonary spirometry showing restrictive pattern
3. HRCT confirming CXR findings plus showing irregularly thickened interlobular septa and intralobular lines.
4. Lung biopsy showing subpleural fibrosis, dense scarring and alternate areas of normal lung tissue & fibroblast proliferation foci. Peripheral cystic dilatations of alveoli (honeycombing) increase with advancing disease.

What can I offer the patient?

1. A mix of corticosteroids and cytotoxic drugs - with the doses regularly titrated depending on how the disease responds.
2. There are a couple of new drugs on the market : Antifibrotic drugs (Pirfenidone and others) and interferon-gamma- 1b have shown promise in certain settings but their true efficacy remains to be established.
3. End of life planning and discussion (median survival is less than 3 years from diagnosis.)

Lung transplant ? only possibly successful in an "otherwise healthy" subgroup of patients < 55 years of age with end stage pulmonary disease. (< 40% of the total IPF population.)

My source for the above info.

BMJ April 14 2007

This week's BMJ is almost like a reminder of first principles in science and medicine.

Firstly, Niell Adhikari and colleagues confirm that in critical care medicine, theoretical hypotheses dont always translate into clinical and practical results. They review the use of Nitric Oxide in acute ling injury and show that depsite the physiological improvements it does not decrease death and conversely causes renal injury,limiting its use for this indication.
So, not everything that is supposed to work - works!

The second article is an incredible, much required review discussing the effect of interventions to improve drinking water on diarrheal diseases. As if to reinforce a point the authors from the London School show that any intervention will reduce the incidence of diarrhea. This review simply goes to show that simple measures are always the best and sanitation the key to all our problems and the most important medical advance over the last 166 years!

Finally, science is complicated enough for us not to make it more complicated with sophisticated biostatistics and data difficult to interpret. This review suggests that use of composite end points in cardiovascular trial points used mainly to decrease sample size might be fraught with its own problems and may lead to data being interpreted the wrong way.

So, when you read an article be careful, be careful when trying to transfer physiological phenomenon to the clinic and stick to the simple interventions - Clean Water!

NEJM -- April 12,2007

New therapies to tackle type -2 diabetes is always a big industry. This week's NEJM publishes a clinical trial using a Interleukin-1 antagonist to improve glycaemic control in DM. Insulin production is increased, beta cell secretory functions are improved and there are very few side effects provided you were willing to inject the drug every day for 13 weeks. Hopefully, further studies might improve the dosing characteristics and lengthen the half life of the drug. If you are a diabetic and wait for a few more years, you might not have to inject insulin anymore, just a IL-1 antagonist.

If you know of patients paying a lot of money in private hospitals after a heart attack to get an operation to put a stent into them,let them know that its not always necessary. More importantly, let the doctors know to have a look at this paper involving over 2000 patients with stable coronary artery disease where percutaneous coronary intervention(PCI) + medical therapy did not have any added benefit over treating such patients by optimal medical therapy alone.

NEJM -- April 12,2007

When we eradicate the world of wild poliovirus and start immunising with injectable polio virus(IPV) instead of Oral Polio Vaccine (OPV), will IPV actually be useful? This study is the first field study to evaluate the efficacy of IPV after eliminating the confounding factors of OPV use and wild type poliovirus infection.

I find this entire area of public health fascinating. Unfortunately for me I was born after global smallpox eradication( I never got a shot) and polio affords me an opportunity to follow the eradication of a disease in real time. I remember giving OPV drops to kids on National Immunisation days while in college but this study addresses a far more important issue.

The WHO in 2004 published a report suggesting the use of IPV following global eradication of polio and the last detectable case of Vaccine-derived poliovirus (VDPV). This is a major policy decision that has to be made and policy and guidelines are being developed since 1998 when the first meeting to discuss post-eradication scenarios took place.

The fundamental issue pertains to the use of any polio vaccine once eradication occurs. The reason OPV is not favoured is because of its propensity to cause VDPV strains which cause poliomyelitis and its ability to spread like wild type poliovirus. So, we use IPV,yes? Not yet, because we dont have enough data about what kind of regimens are efficacious or whether it can prevent an outbreak of wildtype poliovirus. The Cuban study addresses this issue by evaluating IPV efficacy against a challenge of OPV in a setting of 0% prevalence of poliovirus.

The study shows that IPV induces antibodies against the three serotypes of poliovirus but maternal antibodies (induced by OPV vaccination) may decrease protection to poliovirus serotype 2. It also challenges the notion that IPV prevents the excretion of poliovirus and shows that previous data which postulated IPV being as efficacious as OPV might have been influenced by contamination of subjects with either OPV or wild type poliovirus.

What is quite interesting is that although the data suggests that perhaps IPV might not prevent the excretion of poliovirus in stool, it might decrease the amount of poliovirus excreted.

But, lets be realistic about the results. As far as clinical trials for this study is concerned Cuba is a ideal situation and not really representative of countries like India where wild type poliovirus is more prevalent and possibly of higher virulence and therefore the study authors finally suggest careful consideration based on scientific evidence before we blindly substitute OPV for IPV in tropical countries endemic for poliovirus.

If you are interested in this topic also read this Science paper which tackles post-eradication era policies.